Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) in patients with recurrent platinum refractory/resistant ovarian cancer (041)

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Gynecologic Oncology


oregon; portland; chiles; california; santa monica; sjci



Botensilimab (BOT) promotes optimized T-cell priming, activation, and memory formation by strengthening antigen-presenting cell/T-cell co-engagement. As a fragment crystallizable (Fc)-enhanced next-generation anticytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, BOT also promotes intratumoral Treg depletion to improve potency while mitigating difficult-to-treat side effects associated with first-generation CTLA-4 therapy. Results from an expanded phase IA/B study ( NCT03860272 ) in patients with recurrent platinum-resistant/refractory ovarian cancer treated with BOT plus balstilimab (BAL; anti-programmed cell death protein 1 [PD-1]) are presented.


Patients received BOT 1 or 2 mg/kg q6w + BAL 3 mg/kg every 2 weeks. Crossover to combination treatment from BOT monotherapy (rescue) is permitted. Endpoints include incidence of adverse events (AE), objective response rate (ORR; unconfirmed responses included), disease control rate (DCR; the best overall response of either stable disease [SD] or a complete [CR] or partial response [PR]), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Enrollment is ongoing.


Seventeen patients were evaluated for safety and efficacy (treated as of April 7, 2022, with ≥1 q6w tumor imaging assessment), including one rescue patient; data cutoff August 10, 2022. Patients were heavily pretreated, and the median number of prior lines of therapy was 4 (range: 2–7). The most common histology type was high-grade serous. The median duration of study treatment was 3.2 months (range: 0.9–19.6), with a median follow-up of 8.8 months (range: 2.0–29.2). ORR measured 29% (5/17; 95% CI: 13–53; 4 confirmed PRs, 1 unconfirmed CR) (Graph). One patient has an ongoing PR at 24 weeks (−100% reduction of target lesions with residual non-targets), another patient with an unconfirmed CR at 18 weeks developed a solitary new lesion which was radiated and now has no evidence of disease at 90+ weeks, and the rescue patient had prolonged SD on BOT monotherapy for 66 weeks followed by a PR once BAL was added. The safety profile in all 17 patients continues to be favorable, with no cases of hypophysitis, myocarditis, or pneumonitis of any grade. Grade 1/2, 3, or 4 treatment-related adverse events (TRAEs) occurred in 94%, 24%, and 6% of patients, respectively, with no grade 5 TRAEs reported. The only grade 3 or 4 TRAE occurring in more than one patient was diarrhea or colitis (18%). Further evaluation of biomarkers is ongoing, including paired biopsies (before/during treatment).


BOT plus BAL demonstrates meaningful activity in heavily pretreated patients with recurrent platinum-resistant/refractory ovarian cancer who are historically unresponsive to immunotherapy. Randomized studies are planned. Open full size image

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Clinical Institute

Women & Children


Obstetrics & Gynecology